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MiR-493-5p inhibits Th9 cell differentiation in Allergic Asthma by targeting FOXO1
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  • Weili Zhang,
  • Gang Li,
  • He-ting Dong,
  • Hui-ming Sun,
  • Wen-jing Gu,
  • Xin-xing Zhang,
  • Mei-juan Wang,
  • Li Huang,
  • Yong-dong Yan,
  • Chuang-li Hao,
  • Wei Ji,
  • Can-hong Zhu,
  • Zhengrong Chen
Weili Zhang
Children's Hospital of Soochow University
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Gang Li
Children's Hospital of Soochow University
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He-ting Dong
Children's Hospital of Soochow University
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Hui-ming Sun
Children's Hospital of Soochow University
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Wen-jing Gu
Children's Hospital of Soochow University
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Xin-xing Zhang
Children's Hospital of Soochow University
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Mei-juan Wang
Children's Hospital of Soochow University
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Li Huang
Children's Hospital of Soochow University
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Yong-dong Yan
Children's Hospital of Soochow University
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Chuang-li Hao
Children's Hospital of Soochow University
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Wei Ji
Children's Hospital of Soochow University
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Can-hong Zhu
Children's Hospital of Soochow University
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Zhengrong Chen
Children's Hospital of Soochow University
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Abstract

Background:There is an increasing attention on miRNAs because of their functional effect on polarization of CD4+ T cells. This study explores the mechanism of miR-493-5p regulating Th9 cell differentiation in allergic asthma. Methods: The allergic airway inflammation is induced by Ovalbumin(OVA)in mice. CD4+ T cells from normal mice are cultured under Th9 cell conditions. IL-9 levels in mice and CD4+T cells are analyzed by RT-qPCR, ELISA, flow cytometry and western blot. The miR-493-5p levels in mice and cells are detected by RT-qPCR. The interaction between FOXO1 and miR-493-5p is predicted by TargetScan and confirmed by dual luciferase assay. The pathological state is evaluated by H&E staining and Lung resistance is measured in the allergic mice treated with miR-493-5p agomiR before stimulation. Results: The miR-493-5p expression in OVA-induced mice decreases significantly, accompanied by a significant upregulation in IL-9, IRF4 and FOXO1 expression and proportion of CD4+Th9 cells. MiR-493-5p mimic inhibits the expression of IL-9, IRF4 and FOXO1 and Th9 cell differentiation, while the inhibitor promotes these effects. MiR-493-5p mimic represses FOXO1 expression through interacting with 3’UTR of FOXO1 mRNA. The rescue experiment proves that miR-493-5p regulates the differentiation of Th9 cell and the expression of IL-9 by targeting FOXO1. In addition, we find that miR-493-5p agomiR treatment inhibits the FOXO1, IL-9 and IRF4 expression, decreases the proportion of CD4+ Th9 cells, alleviates the pathological state of lung tissue and airway hyperreactivity in OVA-induced asthma mice. Conclusions: Our study confirmed that miR-493-5p inhibited Th9 cell differentiation in allergic asthma by targeting FOXO1.